AVROBIO’s gene therapy holds potential in treating Fabry diseasePublished: February 7, 2019
The clinical-stage biotechnology company AVROBIO has announced interim clinical data from two of its ongoing gene therapy clinical trials for Fabry disease. Data obtained from four patients three months after administering the gene therapy shows positive outcome and favors the therapeutic potential of lentiviral-mediated gene therapy in treating this rare disease.
Fabry disease is an X-linked, rare lysosomal storage disorder caused by a deficiency of alpha-galactosidase A enzyme with the progressive accumulation of globotriaosylceramide in vascular endothelial cells.
In AVROBIO’s lentivirus-mediated gene therapy trials of AVR-RD-01 (an investigator-sponsored Phase 1 study and the AVROBIO-sponsored Phase 2 trial), patient’s stem cells are extracted and genetically modified by adding a functional copy of the GLA gene coding for alpha-galactosidase A. The modified cells are then infused back into the patient via a one-time procedure. The procedure expects to achieve a sustained increase in the enzyme, with the potential to significantly improve patient outcomes and eliminate costly lifetime biweekly intravenous infusions of enzyme replacement therapy (ERT).
The investigator-sponsored Phase 1 study evaluates the safety of AVR-RD-01 in up to six patients with Fabry disease who have been treated with standard of care ERT for at least six months prior to receiving the gene therapy. The company-sponsored Phase 2 trial is an open-label, single-arm clinical trial evaluating the efficacy and safety of gene therapy in eight to twelve patients who have never received ERT (treatment-naive).
6 patients have been dosed thus far in the AVR-RD-01 studies; 4 patients in the Phase 1 study and 2 in the Phase 2 study. Across both studies, 4 patients have reached the point of three-month data analysis or longer after receiving AVR-RD-01; 3 patients in the Phase 1 study and one in the Phase 2 study.
Clinical data from these 4 patients showed sustained AGA enzyme activity above the diagnostic range for males with classic Fabry disease after receiving the gene therapy. The effect of gene therapy on the substrate and metabolite levels were also evaluated and an 85% reduction in lyso-Gb3, an unwanted metabolite that accumulates in the cells of Fabry disease patients, was observed. The gene therapy was also well tolerated in both the trials.
In addition to the clinical updates, AVROBIO has also introduced its new closed, automated vector system for CD34+ cell-based therapies developed to enable worldwide commercialization of the company’s gene therapies. AVROBIO plans to use the plato platform in its gene therapy programs, starting in 2019 with the ongoing Phase 2 clinical program for AVR-RD-01 for Fabry disease and AVR-RD-02 program for Gaucher disease.
Source: AVROBIO, Inc. Announces Updated Clinical Data from Ongoing Phase 1 and Phase 2 Studies for AVR-RD-01 Gene Therapy for Fabry Disease; Press Release